Neuromodulation 2.0: Enabling the Next Generation of Device-Based Therapies for Treating Chronic Diseases

The neuromodulation device industry is enjoying a period of tremendous growth and diversification. A 2016 article by Neurotech Reports estimated the global market for neurotechnology products to be $7.6 billion predicted it will hit $12 billion by 2020. Neuromodulation devices such as neurostimulators targeting the brain, vagus nerve, and spinal cord account for the largest segment and represent some of the most mature applications of neurotechnology for treating diseases such as movement disorders, epilepsy, and pain. However, there are new neuromodulation devices under development aimed at less traditional applications, including sleep apnea, obesity, rheumatoid arthritis and other inflammatory diseases.

Electrode and implantable electronics technologies for neuromodulation devices continue to evolve, but most still lack sufficient efficacy to be considered frontline interventions and are typically implemented as treatments of last resort. Factors limiting adoption are ineffectiveness and off-target effects due to a combination of biological and technological limitations. Further, incomplete knowledge of the physiological mechanisms of neuromodulation makes it difficult to optimize devices and treatment protocols.

Clinically available electrode technologies rely on bulk stimulation of the whole nerve and do not afford precise targeting of select fibers or even fascicles in the nerve. As a result, stimulation parameters are often restricted to a narrow therapeutic window, confined by the need to avoid excessive recruitment of off-target nerves. Most of the existing neuromodulation devices lack sensing capabilities, making it impossible to monitor physiological responses to stimulation as needed to confirm target engagement and enable closed-loop control.

A deeper understanding of the physiology of disease and the direct and downstream effects of neurostimulation are needed to realize the full potential of current and emerging therapies. These knowledge gaps have motivated the creation of large funding initiatives at the National Institutes of Health (NIH) and the Defense Advanced Research Projects Agency (DARPA). The NIH has created the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative and the Stimulating Peripheral Activity to Relieve Conditions (SPARC) program to understand the physiology underlying neurological disease and guide the development of new therapies. DARPA’s Electrical Prescriptions (ElectRx) program is also aimed at understanding biological mechanisms and engineering of new interface technologies that are safer and easier to implant, while increasing precision in accessing therapeutic targets.

Greater knowledge of the underlying biological mechanisms will inform the design and implementation of technologies that provide transformative capabilities in the clinic. More precise targeting capabilities will reduce or eliminate side effects and the addition of sensors and intelligent controllers will yield devices that adapt automatically and continuously to deliver therapies that are personalized to the needs of the individual patient. Taken together, these advances may elevate the status of neuromodulation devices from treatments of last resort to preferred choice, which is timely given the slowing pace and prohibitively high costs of new drug discovery.